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PMID:25242142

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Citation

Voth, W, Schick, M, Gates, S, Li, S, Vilardi, F, Gostimskaya, I, Southworth, DR, Schwappach, B and Jakob, U (2014) The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. Mol. Cell 56:116-27

Abstract

Exposure of cells to reactive oxygen species (ROS) causes a rapid and significant drop in intracellular ATP levels. This energy depletion negatively affects ATP-dependent chaperone systems, making ROS-mediated protein unfolding and aggregation a potentially very challenging problem. Here we show that Get3, a protein involved in ATP-dependent targeting of tail-anchored (TA) proteins under nonstress conditions, turns into an effective ATP-independent chaperone when oxidized. Activation of Get3's chaperone function, which is a fully reversible process, involves disulfide bond formation, metal release, and its conversion into distinct, higher oligomeric structures. Mutational studies demonstrate that the chaperone activity of Get3 is functionally distinct from and likely mutually exclusive with its targeting function, and responsible for the oxidative stress-sensitive phenotype that has long been noted for yeast cells lacking functional Get3. These results provide convincing evidence that Get3 functions as a redox-regulated chaperone, effectively protecting eukaryotic cells against oxidative protein damage.

Links

PubMed PMC4204210 Online version:10.1016/j.molcel.2014.08.017

Keywords

Adenosine Triphosphatases/chemistry; Adenosine Triphosphatases/metabolism; Adenosine Triphosphatases/physiology; Adenosine Triphosphate/metabolism; Guanine Nucleotide Exchange Factors/chemistry; Guanine Nucleotide Exchange Factors/metabolism; Guanine Nucleotide Exchange Factors/physiology; Models, Biological; Molecular Chaperones/metabolism; Molecular Chaperones/physiology; Oxidation-Reduction; Oxidative Stress; Protein Unfolding; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:GET3

enables

GO:0044183: protein folding chaperone

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GET3

enables

GO:0051082: unfolded protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

YEAST:GET3

involved_in

GO:1990507: ATP-independent chaperone mediated protein folding

ECO:0000314: direct assay evidence used in manual assertion

P

part_of:(GO:0034599)

Seeded From UniProt

complete

YEAST:GET3

enables

GO:0051082: unfolded protein binding

ECO:0000314: direct assay evidence used in manual assertion

F

part_of:(GO:0034599)

Seeded From UniProt

complete

Notes

See also

References

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